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Biomedical subjects

Yuichi Ueda

Publications and source records attributed to Yuichi Ueda.

At least 19 recordsLinked to original sources

RhoB is frequently downregulated in non-small-cell lung cancer and resides in the 2p24 homozygous deletion region of a lung cancer cell line.

Identification of a homozygous deletion in cancer cells provides strong evidence for the location of a tumor suppressor gene (TSG). We analyzed the 2p24 homozygous deletion of a non-small-cell lung cancer (NSCLC) cell line, NCI-H2882, and found that the deletion size was 3.7 Mbp. Since RhoB, which has been suggested to be a candidate TSG, was located in this region, we analyzed RhoB for alterations in NSCLC. Although we found no mutations in 48 cell lines including 20 NSCLCs, a loss of heterozygosity (LOH) analysis in 128 primary NSCLCs showed that 25 of 62 informative samples had LOH at the RhoB locus. Northern blot analysis of 28 cell lines (including 15 NSCLCs) indicated that RhoB expression was downregulated in 27. We analyzed RhoB expression in 112 primary NSCLCs with immunohistochemistry and found no or a weak RhoB expression in 33 (42%) of 78 adenocarcinomas, whereas we found it in 29 (94%) of 31 squamous cell carcinomas. No or a weak expression of RhoB was more frequently observed in poorly- or moderately-differentiated adenocarcinomas than in well-differentiated ones (p = 0.0014). Furthermore, no or a weak expression of RhoB indicated a tendency to poor patient prognosis. Although hypermethylation was not found at the promoter region, the RhoB expression in NSCLC cell lines was induced by histone deacetylase inhibition, suggesting that RhoB downregulation may be due to histone modification. The present study demonstrates that RhoB expression is frequently downregulated in NSCLCs by multiple mechanisms, suggesting that RhoB is a candidate TSG for NSCLC.

Aged↗

Mitral valve motion assessed by high-speed video camera in isolated swine heart.

OBJECTIVE: We have recently reported our isolated and working swine heart model that examines the valve motion precisely by a high-speed digital video camera system. Using this modality, the present study aimed (1) to delineate the motion of the mitral leaflets, chords and annulus throughout the cardiac cycle, and (2) to elucidate the influence of alterations in loading conditions on leaflet excursion. METHODS: The valve motion of five isolated and working swine hearts was observed by an endoscope recording the images at 250 frames per second. Modified Krebs-Ringer solution was used as the sole perfusate. The images were obtained in hearts 30 min after reperfusion, changing the left atrial pressure as 4, 8, and 12 mmHg. RESULTS: The motion of the mitral valve in the vicinity of diastole was considered to be well understood by dividing the entire sequence into five stages: 'decoaptation,' 'E excursion,' 'diastasis,' 'A excursion,' and 'coaptation.' Initial separation occurred at both sides of the central tips of the leaflets. The leading edges always followed the mid-portion of the rough zone during opening and closing. The 'strut' second-order chords retained their tension throughout the cardiac cycle and played the role as rotary shafts of the other branching chords. The first-order chords lost their tension during opening, suggesting they mainly are involved in valve competence. Annular constriction occurred coincident with atrial contraction. An increase in preload made the isovolumic relaxation and contraction times shorter. The leaflets opened faster in the rapid-filling phase, whereas they required more time for opening and closing in the atrial-filling phase. CONCLUSIONS: The present study revealed the integrated movement of the mitral leaflets, chords and annulus, as well as the impact of altered preload.

Animals↗

Returning reservoir blood to right atrium during extracorporeal circulation for descending aortic surgery.

We report our techniques on conducting a closed-circuit femoral-femoral bypass during descending aortic surgery by which collected blood can be easily returned into the right atrium. The main circuit was composed of a centrifugal pump, an artificial membrane lung, and a filter. A reservoir with a roller pump was connected to the main circuit via a filter. Extracorporeal circulation was established by right atrial drainage via the femoral vein and femoral arterial return. On aortic cross-clamping, systemic blood pressure was controlled by activating the roller pump in reverse rotation and shifting the body blood into the reservoir temporarily. For a small amount of bleeding after aortotomy, the reservoir blood was returned via the femoral artery by activating the roller pump in normal rotation. When a large amount of bleeding was present making the systemic blood pressure fall, the main circuit was clamped just distal to the centrifugal pump and reservoir blood was directly returned to the right atrium to maintain systemic pressure. Confirming that bleeding was reduced, the clamp distal to the centrifugal pump was gradually released and blood was delivered to both the right atrium and the femoral artery. We believe that our system is a highly beneficial modality.

Aged↗

A vascular tube for intercostal artery reimplantation.

Paraplegia and paraparesis are major concerns in descending and thoracoabdominal aortic repair. A shorter period of spinal cord ischemia is preferred for protection. We have developed a new technique in which plural intercostal arteries are reattached in a short time. The lower descending aorta is tailored using automatic sutures, and a vascular tube is made with diameter about 2.0 cm. Blood supply of intercostal arteries including the Adamkiewicz artery is resumed by perfusing the vascular tube in not more than 20 min. This technique has been applied in four patients, and there was neither paraplegia nor paraparesis.

Aortic Dissection↗

Changing distribution of norovirus genotypes and genetic analysis of recombinant GIIb among infants and children with diarrhea in Japan.

A total of 402 fecal specimens collected during July 2003-June 2004 from infants and children with acute gastroenteritis, encompassing five localities (Maizuru, Tokyo, Sapporo, Saga, and Osaka) of Japan, were tested for the presence of norovirus by RT-PCR. It was found that 58 (14.4%) fecal specimens were positive for norovirus. Norovirus infection was detected throughout the year with the highest prevalence in December. Norovirus GII was the most predominant genogroup (98.3%; 57 of 58). The genotypes detected in this study were GI/4, GII/2, GII/3, GII/4, and GII/6. Of these, NoV GII/3 (known as the Arg320 virus cluster) was the most predominant genotype (43.9%), followed by NoV GII/4 (the Lordsdale virus cluster; 35.1%) and others. Two norovirus strains clustered with a "new variant designated GIIb" and a "new variant of GII/4" were found circulating in Japan for the first time. It was interesting to note that NoV GIIb and NoV GII/3 appeared to be the recombinant strains and the recombination site was demonstrated at the overlap of ORF1 and ORF2. The majority (96%) of the dominant norovirus strains were identified as the recombination of GII/3 capsid and GII/12 polymerase. The recombination in the NoV GIIb capsid gene at the breakpoint located at P1 domain was also identified. Obviously, NoV GIIb isolate in Japan had double recombination. This is the first report demonstrating the existence of different "new variants" co-circulating in Japanese infants and children with acute gastroenteritis.

Base Sequence↗

Surgical treatment for thoracic aortic aneurysm with aberrant right subclavian artery.

We present two operative cases of thoracic aortic aneurysm combined with aberrant right subclavian artery (ARSA). Case 1 was a 71-year-old man with a fusiform-type arch aneurysm. He underwent total aortic arch replacement to reconstruct all 4 arch branches. Case 2 was a 39-year-old man suffering from chronic DeBakey type IIIb dissection. He underwent total descending thoracic aortic replacement for the remaining ARSA. In both cases ARSA was diagnosed preoperatively by reconstructed three-dimensional computed tomography (3D-CT). Both patients followed uneventful postoperative courses with excellent results. 3D-CT is helpful for precise planning of surgical strategy in such cases.

Adult↗

Infective endocarditis with an aortic periannular abscess extending along the right coronary artery.

A 50-year-old male underwent surgery for infective aortic valve endocarditis, which had been refractory to medical treatment. The valve was bicuspid, and involvement of the annular and subannular structures was recognized. A large suppurative discharge was obtained on incising this portion. Although there was no interventricular shunt, the abscess cavity was revealed to extend through the epicardial surface of the right atrioventricular groove. Following extensive debridement and irrigation, the defect was closed by an autologous pericardial patch. A 23 mm mechanical valve was implanted placing some of the stitches deep into the muscular interventricular septum. Infection was controlled by six-week administration of cefazolin sodium and gentamicin sulfate, and the patient survived.

Abscess↗

Development of a novel temporary epicardial pacing wire with biodegradable film.

PURPOSE: A temporary epicardial pacing wire (TEPW) has been routinely placed in patients undergoing cardiac surgery. However, its fixation or removal occasionally causes troublesome complications. The aim of this study is to develop a novel TEPW using biodegradable film to fix the electrode to the epicardium without needle stabbing. DESCRIPTION: A biodegradable film was prepared with poly(L-lactide-co-epsilon-caprolactone). The film has a honeycomb-patterned structure that serves as a temporary adhesive for the myocardial surface, and the electrode was incorporated within the film. The novel TEPW was placed on the ventricular epicardium of dogs (group A, n = 5). As a control, conventional TEPW was inserted (group B, n = 6). The pacing threshold, R wave amplitude, impedance, and slew rate were measured at postoperative days 0, 1, 3, 5, 7, and 14, and complications after removal were checked. EVALUATION: All measurements in both groups were identified and differences were not observed. In addition, the novel TEPWs could be easily removed without related complications. CONCLUSIONS: This novel TEPW is safe and feasible for postoperative management of cardiac surgeries.

Absorbable Implants↗

Late mortality and morbidity in elderly patients with mechanical heart valves.

A retrospective study was performed in patients under and over 65 years old implanted with a mechanical valve, to compare late mortality and morbidity. Of 381 patients who underwent mechanical valve replacement at Nagoya University in the 1990s, 357 (11 hospital deaths and 13 lost to follow-up; 96.4% follow-up rate) were followed up for 7.9 +/- 3.3 years (2,811 patient-years). They were divided into two groups either side of 65 years of age at operation. The young and elderly patient groups contained 275 and 82 patients, respectively. The survival rate in the young group was 96.1% (95% confidence interval, 93.7%-98.5%) at 5 years and 92.0% (95% confidence interval, 88.3%-95.7%) at 10 years, which was significantly better than 88.0% (95% confidence interval, 80.6%-95.4%) at 5 years and 73.8% (95% confidence interval, 66.2%-85.4%) at 10 years in the elderly group. The two groups did not differ significantly in the incidence of thromboembolic events, bleeding events, endocarditis, or reoperation. We are also encouraged by the fact that mechanical valves are not a risk factor for late mortality or morbidity, even in elderly patients.

Age Factors↗

Clinical characteristics of bicuspid aortic valves in surgical patients.

Of 413 patients undergoing surgery for aortic valve disease, 42 were confirmed to have congenital bicuspid aortic valve. There were 24 males and 18 females, with a mean age of 54.9 +/- 14.6 years. The etiology of the surgical indications in patients with bicuspid valves were degeneration, rheumatic disease, and infectious endocarditis. Thirty-two patients had aortic stenosis and 10 had aortic regurgitation. Infective endocarditis was seen mainly in patients < or =50 years of age at the time of surgery, while degenerative aortic stenosis occurred more often in older patients. The annular diameter measured during surgery was significantly narrower in the 42 patients with bicuspid valves compared to 371 patients with tricuspid valves who underwent aortic valve replacement during the same period. It is important to prevent infectious endocarditis in younger patients diagnosed with bicuspid aortic valve, whereas careful attention should be paid to decalcification during surgery in older patients because the vast majority suffer from degenerative aortic stenosis.

Adolescent↗

Mitral valve surgery for dilated cardiomyopathy with mitral regurgitation.

Outcomes of surgery for non-ischemic non-valvular dilated cardiomyopathy with associated mitral regurgitation were assessed in 8 consecutive patients who underwent 9 mitral valve operations between 2001 and 2004. Mitral valve replacement was performed when the coaptation depth exceeded 10 mm. Two patients initially underwent mitral valvuloplasty, and 6 underwent valve replacement. One patient had valve replacement soon after valvuloplasty. Transthoracic echocardiography was performed immediately before surgery, before discharge, and during follow-up. Transesophageal echocardiography was carried out intraoperatively to assess valvular and ventricular function. Postoperative mean functional class was significantly better than the preoperative value (2.4 +/- 0.7 vs. 3.3 +/- 0.7), and the improvement was sustained during follow-up (2.0 +/- 0.7). The ejection fraction and left ventricular end-diastolic dimension did not improve. One patient died without leaving hospital and two died during follow-up. The 2- and 4-year survival rates were 75.0% and 37.5%. Mitral valve surgery improved functional class without obvious changes in ejection fraction or left ventricular end-diastolic dimension.

Adult↗

Clinical protocol for angiogenesis by intramyocardial injection of autologous bone marrow mononuclear cells in patients with severe coronary artery disease: TACT-NAGOYA-HEART.

BACKGROUND: Despite recent improvements in the treatments of coronary artery disease (CAD), there are a considerable number of patients who can not receive complete revascularization because of severe or total arterial occlusion. Intramyocardial injection of autologous bone marrow mononuclear cells (ABMMCs) has been shown to induce neovascularization of ischemic myocardium. METHODS AND RESULTS: The study will investigate the safety and feasibility of intramyocardial injections of ABMMCs and test the hypothesis that this treatment would promote neovascularization and improve left ventricular (LV) global and/or regional function in patients with severe CAD who have no other option. ABMMCs (approximately 10(6) cells) will be injected into the area of ischemic myocardium where the coronary artery is not graftable, in combination with bypass surgery to the other coronary branches. Myocardial perfusion and LV global and regional function will be evaluated, based on the micromanometer-tipped catheter method, single-photon emission tomography, and myocardial enhanced and color tissue Doppler echocardiography at baseline and during 12 month follow-up. CONCLUSIONS: This project will demonstrate that intramyocardial injection of ABMMCs with or without coronary artery bypass surgery could be a safe and effective method for therapeutic neovascularization, resulting in an improvement of cardiac function in patients with severe CAD.

Bone Marrow Cells↗

Measurement of cerebral-oxygenation status when commencing cardiopulmonary bypass in pediatric open-heart surgery.

OBJECTIVE: We hypothesize that there is a difference in the cerebral-oxygenation status between cyanotic and non-cyanotic congenital heart disease when commencing a crystalloid-primed cardiopulmonary bypass (CPB). We tested this hypothesis by using near-infrared spectroscopy (NIRS). METHODS: Group 1 consisted of ten patients with non-cyanotic congenital heart diseases, including atrial septal (n=4) and ventricular septal defects (n=6), while group 2 consisted of ten patients with cyanotic congenital heart diseases, including tetralogy of Fallot (n=7) and univentricular heart (n=3). Changes in cerebral-oxygenated, deoxygenated and total hemoglobin concentrations were measured by NIRS just before and every minute for the first 10 min after commencing CPB. Arterial blood analysis was performed at those same time times. RESULTS: NIRS showed a rapid fall and plateauing of cerebral-oxygenated, deoxygenated and total hemoglobin in group 1. However, although group 2 showed a rapid fall and plateauing of cerebral-oxygenated hemoglobin, a rapid fall and continuous gradual decrease in cerebral-deoxygenated and total hemoglobin were also seen. Cerebral-deoxygenated and total hemoglobin decreased more markedly in group 2 than in group 1 (P<0.001, 0.01, respectively). CONCLUSION: NIRS revealed that the cerebral-oxygenated hemoglobin could be maintained at a similar level at the beginning of CPB in both groups. However, it showed a different distribution of cerebral-deoxygenated and total hemoglobin between the groups. An inadequate cerebral-oxygenation status may occur in the early phase of CPB in patients with cyanotic congenital heart diseases.

Analysis of Variance↗

Detection and genetic characterization of norovirus strains circulating among infants and children with acute gastroenteritis in Japan during 2004-2005.

A total of 752 fecal specimens collected during the period of July 2004 to June 2005 from infants and children with acute gastroenteritis from four different regions (Maizuru, Tokyo, Sapporo, and Osaka) of Japan were tested for the presence of norovirus by RT-PCR. It was found that 139 (18.5%) fecal specimens were positive for norovirus. Norovirus infection was detected almost all year round with the highest prevalence in January. Norovirus GII was the most predominant genogroup (98.6%; 137 of 139). The genotypes detected in this study were GI/1, GII/1, GII/3, GII/4, and GII/6. Of these, NoV GII/4 (known as the Lordsdale virus cluster) was re-emerging and became the leading genotype (77.7%). Meanwhile, the incidence of NoV GII/3 (known as the Arg320 virus cluster) has dropped rapidly, accounting for only 15.8%. Another interesting feature of the study was the identification of Picton03/AU-like recombinant NoV for the first time in Japan. Based on the genetic analysis, it was interesting to note that NoV GII/4 in 2004-2005 made a distinct cluster in comparison to other NoV GII/4 circulating in 2002-2003 and 2003-2004. Of note, "new recombinant variant designated GIIb" within NoV GII/3, which was first detected in Saga City, Japan in 2003-2004 in only one case, had increased, spreading widely in Japan and representing 45.5% (10 of 22). Further epidemiological studies should be conducted to determine whether this new recombinant variant strain will be dominant in Japan in the coming year.

Acute Disease↗

Surgery for calcific aortic root stenosis in homozygous familial hypercholesterolemia.

A 35-year-old female with homozygous familial hyperlipidemia (IIa) was referred to our hospital for an operation against supravalvular and valvular aortic stenosis. She had been treated with low-density lipoprotein apheresis for 20 years, and total cholesterol ranged between 200 and 400 mg/dl under this treatment. She had undergone percutaneous coronary intervention for ostial stenosis of the right coronary artery three times since the age of 19. Unenhanced three-dimensional computed tomography showed supravalvular stenosis, funnelling and heavily calcified aorta. An operation was performed under deep hypothermic circulatory arrest without aortic cross clamping. After the ascending aorta had been replaced with a one-branched vascular graft, arterial perfusion was resumed. The stenosed ascending aorta was resected at the sinotubular junction. Because the aortic root was still extremely small, the noncoronary sinus and the commissure between left and right coronary cusp were incised, and the aortic root was enlarged with linguiform vascular-graft patches. A 21-mm mechanical valve was implanted. The postoperative course was uneventful.

Adult↗